The findings summarized in the prior sections demonstrate that the maternal infection and MIA models display face (similar symptoms) as well as construct (similar cause) value for both autism and schizophrenia. These models can have predictive value as well. For example, the manipulation of cytokines during pregnancy can prevent the development of abnormal behaviors in the offspring in the poly(I:C) and LPS models. In addition, pretreatment of pregnant rats with N-acetyl-cysteine, which increases calcium influx when binding to glutamate receptors in combination with the transmitter, and also suppresses fetal inflammatory responses to LPS, prevents many of the effects of maternal LPS administration (4
). The ability of IL-10 to block the effects of MIA is an attractive intervention because endogenous IL-10 is essential for resistance to LPS-induced preterm labor and fetal loss. Thus, administration of this cytokine enhances a natural protective mechanism. However, increased IL-10 in the absence of MIA in pregnant mice can lead to behavioral abnormalities in the adult offspring (30
), a finding consistent with the fact that normal human pregnancy involves increased inflammation. Therefore, postnatal cytokine perturbations would potentially be a safer therapeutic approach. It is also clear that postnatal cytokine manipulations can induce behavioral changes in the absence of MIA (40
). Such manipulations in MIA models could be a fruitful area of research.
In fact, MIA models have proven valuable for testing other types of postnatal therapies. Whereas acute antipsychotic drug administration in adult influenza and poly(I:C) MIA offspring can ameliorate some of the behavioral deficits (4
), administration of such medications in immature MIA offspring, before the onset of behavioral abnormalities and ventricular enlargement, is effective in preventing the onset of such symptoms (41
). Treatment for a week during adolescence, many weeks before beginning behavioral testing, prevents the onset of abnormalities and the ventricular enlargement. Therefore, despite the fact that MIA has induced many changes in the brain during fetal development, postnatal behaviors can be subsequently altered. Although the classic action of these antipsychotic medications involves blockade of the D2 dopamine receptor in the brain, it is also worth noting in the present context that many of them have also been shown to influence cytokine expression in peripheral immune cells (4
It is also important to note, in the context of potential postnatal treatments, that in mouse models of a number of rare genetic disorders with autistic symptoms such as fragile X, Rett syndrome and TSC, behavioral abnormalities can be at least partially reversed in adulthood. These findings have led to several clinical trials in these disorders (43